Codegoni A M, Broggini M, Pitelli M R, Pantarotto M, Torri V, Mangioni C, D'Incalci M
Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Gynecol Oncol. 1997 Apr;65(1):130-7. doi: 10.1006/gyno.1996.4609.
The expression of different genes potentially involved in DNA repair and in cell responses to chemotherapy was evaluated in 33 previously untreated ovarian cancer patients. In biopsies of the same patients the expression of repair genes O6-methylguanine DNA methyltransferase (MGMT), 3-methyladenine DNA glycosylase (MAG), ERCC1, MDR-1, DNA topoisomerase I, DNA topoisomerase IIalpha, and glutathione S-transferase-pi (GST-pi) was assessed by Northern blot analysis. No direct statistical correlation was found between the expression of these genes and the response to chemotherapy (mainly platinum-based with or without doxorubicin and cyclophosphamide). Univariate analysis showed a weak negative correlation (P = 0.037) between the expression of ERCC1 and mortality, whereas no statistically significant correlation was found for other parameters. The MDR-1 gene encoding for the P-glycoprotein P-170 was mostly undetectable in these patients (as assessed by Northern blotting), whereas relatively high levels of MAG and MGMT were found in the majority of patients. A statistically significant correlation was found between the expression of DNA topoisomerase I and the expression of either ERCC1 (P = 0.0026) or GST-pi (P = 0.0279).
在33例未经治疗的卵巢癌患者中，评估了可能参与DNA修复及细胞对化疗反应的不同基因的表达情况。通过Northern印迹分析，对同一批患者活检样本中修复基因O6-甲基鸟嘌呤DNA甲基转移酶（MGMT）、3-甲基腺嘌呤DNA糖基化酶（MAG）、ERCC1、多药耐药基因1（MDR-1）、DNA拓扑异构酶I、DNA拓扑异构酶IIα和谷胱甘肽S-转移酶π（GST-π）的表达进行了评估。未发现这些基因的表达与化疗反应（主要是含或不含阿霉素及环磷酰胺的铂类化疗）之间存在直接的统计学相关性。单因素分析显示，ERCC1的表达与死亡率之间存在微弱的负相关性（P = 0.037），而其他参数未发现有统计学意义的相关性。编码P-糖蛋白P-170的MDR-1基因在这些患者中大多检测不到（通过Northern印迹法评估），而大多数患者中发现MAG和MGMT的水平相对较高。DNA拓扑异构酶I的表达与ERCC1（P = 0.0026）或GST-π（P = 0.0279）的表达之间存在统计学显著相关性。
